The long-term goal of this research program is to define the molecular and conformational links between the absorption of light by rhodopsin in the disc membrane and the subsequent change in the sodium permeability of the plasma membrane. Three major lines of research are in progress: (1) We have found that several proteolytic enzymes cleave rhodopsin in retinal disc membranes into large fragments, F1 and F2, which can be solubilized in detergent as a non-covalent complex. The complex of F1 and F2 exhibits 500 nm absorbance and is regenerable after bleaching. Most interesting, light dissociates F2 from F1. We are carrying out chemical studies of F1 and F2, and investigating the possibility that the photodissociation of F1 and F2 is an expression of a critical conformational change in visual excitation. (2) We have devised a new method for obtaining the resonance Raman spectrum of a photolabile molecule before it is modified by light, which we have used to measure the resonance Raman spectrum of rhodopsin. We are carrying out rapid-flow studies of photolytic intermediates to delineate the conformational changes in the retinal chromophore following the absorption of a photon. (3) We are carrying out neutron diffraction studies of intact retinas at Brookhaven National Laboratory. Our low-resolution Fourier shows that rhodopsin is an elongated molecule and that about two-thirds of it extends from the cytoplasmic face of the membrane into the aqueous region between discs. BIBLIOGRAPHIC REFERENCES: Pober, J.S. and Stryer, L., Light dissociates enzymatically-cleaved rhodopssin into two different fragments, J. Mol. Biol. 95: 477-481(1975). Renthal, R., Pober, J.S., Steinemann, A., and Stryer, L., Concanavalin A-agarose in the study of rhodopsin and its derivatives, in "Concanavalin A as a Tool" (ed. by H. Bittiger and H.P. Schnebli, Wiley, 1975).